DESCRIPTION: Hemochromatosis refers to a state of iron overload. Numerous cellular changes from altered gene expression to oxidative cellular damage and cytotoxicity have been observed in iron-loaded livers of hemochromatosis patients. Eventually, chronic iron overload leads to fibrosis. The liver becomes cirrhotic and hepatocarcinomas may arise. Dr. Isom's goal is to addres the isolated issue of how iron overload alters the function of well-differentiated hepatocytes in the absence of other cell types. The hypothesis being tested is: Iron loading of hepatocytes in long-term DMSO culture induces specific types of cellular damage that are potentated if the cells are treated with cytokines. Iron overloaded hepatocytes in long term DMS culture will be used: 1) to determine what types of cellular damage occur in acute and chronic iron overloaded hepatocytes; 2) to determine whether the method by which iron is taken up by hepatocytes or the antioxidant environment of the hepatocyte in the process of iron overload affects the reversibility of the iron overload process and/or the type and extent of cellular damage; and 3 to determine the effect of TNF alpha treatment on cellular injury, expression of ferritin and other gene products associated with iron homeostasis in iron overloaded hepatocytes.